This study aims to analyse the tolerability (side effects and safety) with standard treatment (Javlor®) with the addition of a second anti-tumour drug: sorafenib (Nexavar®). This is the first time this treatment combination is studied in humans. Samples of blood, urine and tumour tissues will be analysed for molecular biomarkers. These biomarkers may potentially help us in the future in predicting whether a patient will benefit or not from the cancer treatment. The study also aims to investigate if a newer imaging method, called PET-CT (positron emission tomography-computed tomography), at an earlier stage (than a normal CT scan) can identify patients who will benefit from the given treatment.

For patients with PS 1, or age 75 to 80 years, or exposed to radiation of the lower pelvis region, or with impaired renal function (creatinine clearance 40-60 ml/min) but adequate hepatic function (as described in the inclusion criteria), the dose of vinflunine is 280 mg/m2 I.V. day 1, repeated every 21 days.

Other Name: Javlor

Drug: Sorafenib

Sorafenib (Nexavar®, Bayer HealthCare) daily dosage from day 2 through day 21 (repeated every 21 days):

To explore the safety of sorafenib in combination with vinflunine in patients with transitional cell carcinoma of the urothelial tract and to define a recommended phase II dose for this treatment combination

To correlate early tracer 18F-FDG-PET/CT functional imaging readouts with standard RECIST (version 1.1) evaluations with the intention to explore new endpoints for targeted therapy

To evaluate serum and urine markers of apoptosis as potential markers of sorafenib/vinflunine treatment

Rationale/Goal

To evaluate the tolerability and activity of sorafenib combined with vinflunine in patients with advanced or metastatic urothelial cancer.

Tumour biopsies will be collected before and after one cycle of therapy. The translational part of this study aims to explore the predictive value of a number of biomarkers related to the targeted properties of sorafenib and presumptive markers for vinflunine treatment.

In addition, the predictive value of an early functional imaging tracer 18F-FDG-PET/CT will be evaluated.

patients who have received neoadjuvant or adjuvant platinum-containing chemotherapy and who are diagnosed with locoregional recurrent or metastatic disease prior to or at the 6-months‟ visit , are eligible or

patients who have received palliative platinum-containing chemotherapy and who are diagnosed with progression prior to or at the 6-months‟ visit, are eligible or

patients who have contraindication to platinum-containing chemotherapy;

previous systemic chemotherapy must have been stopped 14 days before the inclusion with recovery (G1 or less) from any treatment related toxicity;

measurable and/or non-measurable disease using RECIST and defined as: Measurable disease: lesions that can be measured in at least one dimension and which have not been previously irradiated. Longest diameter 20 mm with conventional techniques or 10 mm with spiral CT scan or MRI. Non-measurable disease: lesions which have not been previously irradiated, or longest diameter <20 mm with conventional techniques or <10 mm with spiral CT scan or MRI, or truly non measurable lesions including bone lesions, ascites, pleural/pericardial effusion, and lymphangitis cutis/pulmonitis;

known or suspected allergy to the investigational agent or any agents given in association with this trial;

current medical treatment with any compound that prolongs QTc

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01844947